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PubMed1996

Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients.

The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.

Adult↗

PubMed1998

Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant.

We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable. A renal biopsy showed massive tubular necrosis associated with a prominent granulomatous reaction. The process had a striking regional distribution within the kidney with the injury and inflammation limited to the outer medulla. Adenovirus type 11 was isolated from renal tissue by culture, and adenovirus was demonstrated by immunofluorescence and electron microscopy in the kidney biopsy. Immunosuppression may result in unusual patterns of response to infectious agents. This case demonstrated tropism of the adenovirus to only selected tubules within the kidney, with sparing of other organ function including, specifically, the pancreas allograft. The differential diagnosis of a granulomatous reaction in the transplant kidney must be expanded to include viral infection, in particular, adenovirus.

Adenovirus Infections, Human↗

PubMed1990

Glomerulotubular function in long-term renal allograft recipients. A comparison of conventional therapy with cyclosporine.

Glomerular and tubular function were assessed, using a lithium clearance technique, in two groups of renal allograft recipients at least one year after transplantation. Group 1 comprised 14 patients receiving low-dose prednisolone and cyclosporine, and group 2, 14 patients receiving low-dose prednisolone and azathioprine. There were no significant differences in creatinine clearances between the two groups, although the clearances of lithium (which is absorbed almost exclusively from the proximal tubule) and sodium were significantly lower in the cyclosporine-treated group. Fractional lithium excretion was also significantly lower in group 1 than in group 2, but there was no significant difference in fractional sodium excretion. The absolute proximal reabsorption of sodium and water did not differ between the groups, although the fractional proximal reabsorption of sodium and water was significantly higher in group 1. In contrast, the distal reabsorption of sodium and of water was significantly lower in the cyclosporine-treated patients than in the azathioprine-treated patients; there were, however, no significant differences in the distal fractional reabsorptions of sodium and water between the two groups. In addition there was no correlation in group 1 between whole-blood cyclosporine levels or time since transplantation and any of the assessed parameters of renal function. These results indicate that tubular concentrating abnormalities in cyclosporine-treated renal allograft recipients are similar to those observed in rodent models of cyclosporine nephrotoxicity. They suggest that the pathogenesis of cyclosporine nephrotoxicity may be similar in renal allograft recipients to that in experimental models.

Adult↗

PubMed1981

Fat clearances and hyperlipidaemia in renal allograft recipients--the role of insulin resistance.

The mechanism of hyperlipidaemia in renal allograft recipients was investigated in 19 patients randomly selected from a cohort of 54 patients with functioning renal allografts. Serum cholesterol, triglyceride and high-density lipoprotein cholesterol concentrations as well as plasma immunoreactive insulin levels were measured in fasting blood samples. Intravenous fat tolerance tests were performed before and 15 min after heparin administration. Renal allograft recipients had reduced fractional clearance rates of Intralipid and a positive correlation was demonstrated between plasma immunoreactive insulin levels and serum triglyceride concentrations. Plasma immunoreactive insulins also correlated inversely with fractional clearance rates of Intralipid. It was concluded that both increased production and decreased removal of lipoproteins contribute to the hyperlipidaemia and that insulin resistance due to corticosteroids was the centre of the problem.

Adult↗

PubMedDate not supplied

Comparison of Duplex sonography and color Doppler imaging in renal allograft evaluation: a prospective study.

A prospective study compared the diagnostic capability of quantitative Duplex sonography (DS) and color Doppler imaging (CDI) in 49 consecutive patients with 50 renal allografts. Sixty five DS examinations and 65 CDI examinations were performed by two independent investigators on two different machines on the same day. The resistive index (RI) was calculated and the color flow of renal arteries was observed up to the arcuate arteries. There was good correlation of RI values obtained by DS and CDI at all vascular sites. Thirty one allografts were functioning stably and 19 were in a state of dysfunction, defined by histology (n = 17). Forty allografts presented with a RI less than 0.9 and normal color flow. All five allografts with a pathologic RI greater than or equal to 0.9 showed abnormal color flow (missing flow in arcuate and/or interlobar arteries). Five allografts had a RI less than 0.9 but abnormal color flow, possibly due to atrial fibrillation, hypertension, heart failure or a combination of these. A normal color flow pattern excludes severe vascular compromise to the allograft. In addition, CDI revealed three biopsy-related vascular lesions; two of them had been missed by DS.

Adult↗

PubMed1999

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

BACKGROUND: Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. PATIENTS: We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. RESULTS: Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). CONCLUSIONS: Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

Adult↗

PubMed1997

Kidney-alone transplantation in diabetic patients with end-stage renal disease.

From January 1989 to December 1995, 5 diabetic patients with end-stage renal disease (1 woman, 4 men) underwent kidney-alone transplantation. The mean age of the recipients at the time of transplantation was 37.4 years (range, 32 to 43). Craft function and glucose tolerance was evaluated for 5 to 72 months after surgery. Postoperative complications were seen in 2 patients; nonspecific subcutaneous infections and an asymptomatic partial allograft infarction. All renal allografts were functioning 1 year after transplantation, with a mean serum creatinine level of 1.10 mg/dL (range, 0.8 to 1.8 mg/dL), and a mean urinary protein level of 17.8 mg/dL (range, 5 to 27 mg/dL). The postoperative daily dose of insulin was higher than the preoperative dose, while the level of glycated hemoglobin (HbA1C) increased after surgery and peaked 6 months after transplantation; 1 year after transplantation it had reverted to the preoperative level. As long as the diabetic complications of the renal allograft recipients are not severe, the short-term survival and the renal function of diabetic patients with end-stage renal disease improves after kidney-alone transplantation, which is still the standard method of treatment in Japan.

Adult↗

PubMed1991

Noninvasive assessment of cardiac transplant rejection. A critical look at the approach to acute rejection.

The diagnosis of acute rejection remains a key issue in the management of the heart transplant recipient. Myocardial biopsy for tissue examination is the basic step for screening and diagnosis of acute rejection. Although endomyocardial biopsy is reliable, it is an inefficient approach to screening after transplantation and yielded only a 14% rate of positive results in the author's experience, from 1983 to 1990, of 568 biopsies. A reliable noninvasive method for screening acute rejection is therefore needed. Numerous noninvasive methods have been studied to monitor the systemic immune process against the allograft or to evaluate the effect of rejection on graft function and status. For 13 methods of evaluating immune process against the allograft the sensitivity and specificity ranged from 13% to 95% and 19% to 94% respectively. For nine methods of evaluating allograft function, sensitivity and specificity ranged from 60% to 93% and 65% to 97% respectively. Overall, methods monitoring allograft function and status have better results in predicting acute rejection. Nevertheless, the author estimated that 15 episodes of acute rejection would have been missed by these monitoring methods in his group of patients.

Acute Disease↗

PubMed1983

Chronobiology in hematology and immunology.

The hematopoietic and the immune systems in all their components are characterized by a multifrequency time structure with prominent rhythms in cell proliferation and cell function in the circadian, infradian, and rhythms in cell proliferation and cell function in the circadian, infradian, and circannual frequency ranges. The circulating formed elements in the peripheral blood show highly reproducible circadian rhythms. The timing and the extent of these rhythms were established in a clinically healthy human population and are shown as chronograms, cosinor summaries and, for some high-amplitude rhythms, as time-qualified reference ranges (chronodesms). Not only the number but also the reactivity of circulating blood cells varies predictably as a function of time as shown for the circadian rhythm in responsiveness of human and murine lymphocytes in vitro to lectin mitogens (phytohemagglutinin and pokeweed mitogen). Some circadian rhythms of hematologic functions appear to be innate and are presumably genetically determined but are modulated and adjusted in their timing by environmental factors, so-called synchronizers. Phase alterations in the circadian rhythms of hematologic parameters of human subjects and of mice by manipulation of the activity-rest or light-dark schedule and/or of the time of food uptake are presented. Characteristically these functions do not change their timing immediately after a shift in synchronizer phase but adapt over several and in some instances over many transient cycles. The circadian rhythm of cell proliferation in the mammalian bone marrow and lymphoid system as shown in mice in vivo and in vitro may lend itself to timed treatment with cell-cycle-specific and nonspecific agents in an attempt to maximize the desired and to minimize the undesired treatment effects upon the marrow. Differences in response, and susceptibility of cells and tissues at different stages of their circadian and circaseptan (about 7-day) rhythms and presumably of cyclic variations in other frequencies are expected to lead to the development of a chronopharmacology of the hematopoietic and immune system. Infradian rhythms of several frequencies have been described for numerous hematologic and immune functions. Some of these, i.e., in the circaseptan frequency range, seem to be of importance for humoral and for cell mediated immune functions including allograft rejection. Infradian rhythms with periods of 19 to 22 days seem to occur in some hematologic functions and are very prominent in cyclic neutropenia and (with shorter periods) in its animal model, the grey collie syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed2005

Split-liver transplantation: results of statewide usage of the right trisegmental graft.

Split-liver transplantation (SLT) effectively expands the cadaveric donor pool for children. The remaining right trisegmental (RTS) graft can be transplanted into adults. Limited information exists regarding the outcomes of RTS allografts. Sixty-five RTS graft recipients from five adult transplant programs in Texas were identified. Donor and recipient information were analyzed retrospectively. Most livers (75%) were originally allocated to pediatric recipients. Liver splitting occurred via the in situ (72%) and ex situ (28%) techniques. Arterial reconstruction of RTS grafts was common (52%). Patient and graft survival at 3 months were comparable for the in situ and ex situ techniques (p = 0.2). Cox regression showed only in situ splitting to be a predictor of outcome longer than 3 months posttransplant. Sharing of grafts between centers was frequent (37% of total). One-year patient and allograft survival (87.1% and 85.4%) were excellent with no cases of primary nonfunction. SLT consistently generates two functional liver allografts with excellent recipient survival. In situ splitting of the liver is the preferred technique. Decreased survival is observed with RTS graft use in higher risk recipients. Broader application of SLT with increased sharing is feasible and safely expands the number of liver allografts that can be transplanted.

Adult↗

PubMedDate not supplied

A morphological assessment of vein allografts preserved in glycerol and used for arterial replacement.

There is an increasing need for alternatives to reversed autogenous saphenous vein in the treatment of first-time and recurrent arterial occlusions. Vein grafts taken from rats and goats and from humans were preserved in glycerol, reconstituted in saline and compared morphologically with fresh veins of similar origin. In rats and goats, autograft, allograft and glycerol-preserved allograft veins were used to replace lengths of common iliac and carotid arteries. After various periods of time these were retrieved and examined using light microscopy and scanning electron microscopy. Appearances were found to correlate well with function. All allograft vessels were found to have failed. Over 70% of autografts were functional in both species and all of these had re-endothelialised. In rats, all of the glycerol-preserved grafts had failed but in goats 64% were patent at 6 months but did not show signs of a neointima. In larger animals, glycerol-preserved vein allografts appear to offer an acceptable form of arterial replacement where fresh vein autograft is unavailable.

Animals↗

PubMed1987

Liver transplantation before 1 year of age.

Since 1981, 20 infants younger than 1 year of age received 26 orthotopic liver transplants. Immunosuppression was with cyclosporine and corticosteroids. Thirteen (65%) of the recipients were discharged from the hospital. To date, 12 (60%) of the 20 recipients are surviving, with follow-up of 1 to 56 months (average 14 months). The 5-year actuarial survival is 53.8%. The allograft liver function in the majority of surviving infants is excellent. The predominant causes of mortality were primary nonfunction of the allograft (three patients) and sepsis (three). Major morbidity was caused by hepatic artery thrombosis (five patients), gastrointestinal complications (six), biliary tract complications (five), and bacterial and viral infections (13). Six patients underwent retransplantation; three of these six survived. Results could be improved by prevention of hepatic artery thrombosis, by decreasing the incidence of sepsis, and by procurement of more and better suited pediatric donors.

Actuarial Analysis↗

PubMed1988

The influence of kidney transplantation on carnitine metabolism.

In this study, we examined all three plasma carnitine fractions, free carnitine (FC), short-chain acyl- (SCC), and long-chain acylcarnitine (LCC), as well as the urinary excretion of FC and SCC in 62 patients with functioning renal allografts 1-70 months following the kidney transplantation (KT). Patients were classified into three groups according to their transplant function, as characterized by the serum creatinine concentration (CR). A comparison with normal subjects (n = 20) and with patients on chronic hemodialysis (HD, n = 46) revealed a complete normalization of all carnitine plasma fractions for group I patients (Cr less than 120 mumol/l). In contrast, significant elevations of plasma free and esterified carnitine were found in group II (Cr greater than 120, less than 200 mumol/l; with FC + 27%, SCC + 82%, and LCC + 49% and group III patients (Cr greater than 200 mumol/l; with FC + 39%, SCC + 122%, and LCC + 106%), as compared to healthy subjects (p less than 0.001). The elevations in concentrations of SCC were more pronounced than those of FC; consequently, we found a higher ratio of acylcarnitine (AC) to FC in group III than in group I patients (+ 41%, p less than 0.001). Yet even in the former group, this ratio was found to be markedly reduced when compared to HD patients (-41%, p less than 0.001). We found no significant differences in the urinary excretion of FC and SCC between the 3 groups of KT patients. It is thus to conclude that in patients with a well-functioning transplant, the pattern of carnitine fractions in plasma is fully normalized. The decrease in the ratio of AC to FC following a successful KT might suggest a better availability of FC and thereby be associated with an enhanced fatty acid oxidation.

Acetylcarnitine↗

PubMed2004

Transplant graft vasculopathy: an emerging target for prevention and treatment of renal allograft dysfunction.

Maintenance of healthy endothelium is essential to vascular homeostasis, and preservation of endothelial cell function is critical for transplant allograft function. Damage of microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection and chronic allograft nephropathy, which is an important predictor of graft loss and is often associated with transplant vasculopathy. In this review, we will discuss the role of microvascular endothelium, in renal allograft dysfunction, particularly as it relates to markers of endothelial dysfunction and endothelial repair mechanisms. We also discuss the potential for therapies targeting endothelial dysfunction and transplant graft vasculopathy.

Humans↗

PubMed1983

Lung transplantation in the rat. III. Functional studies in iso- and allografts.

Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research.

Animals↗

PubMed1977

Influence of viability on canine allograft heart value structure and function.

A study was undertaken to determine whether, in antibiotic sterilised and stored valves, the state of preimplantation leaflet viability could be shown to influence valve structure and function following isotopic allotransplantation in dogs. Fourteen viable and 12 nonviable valves were assessed after periods of up to 8 weeks' implantation. Assessment of valve structure was made macroscopically with measurement of leaflet surface areas, and microscopically. Pressure measurements were made across the allografted valve both at insertion and at removal. The results of this study indicate that preimplantation viability results in gross valve leaflet distortion and shrinkage with consequent loss of function. Nonviable valves, in contrast, showed minimal alteration in valve dimensions with retention of normal function. These findings have considerable implications in the preparation and clinical use of allograft heart valves.

Animals↗

PubMed2003

Molecular profiling of anemia in acute renal allograft rejection using DNA microarrays.

Compromised renal function after renal allograft transplantation often results in anemia in the recipient. Molecular mechanisms leading to anemia during acute rejection are not fully understood; inadequate erythropoietin production and iron deficiency have been reported to be the main contributors. To increase our understanding of the molecular events underlying anemia in acute rejection, we analyzed the gene expression profiles of peripheral blood lymphocytes (PBL) from four pediatric renal allograft recipients with acute rejection and concurrent anemia, using DNA microarrays containing 9000 human cDNA clones (representing 7469 unique genes). In these anemic rejecting patients, an 'erythropoiesis cluster' of 11 down-regulated genes was identified, involved in hemoglobin transcription and synthesis, iron and folate binding and transport. Additionally, some alloimmune response genes were simultaneously down-regulated. An independent data set of 36 PBL samples, some with acute rejection and some with concurrence of acute rejection and anemia, were analyzed to support a possible association between acute rejection and anemia. In conclusion, analysis using DNA microarrays has identified a cluster of genes related to hemoglobin synthesis and/or erythropoeisis that was altered in kidneys with renal allograft rejection compared with normal kidneys. The possible relationship between alterations in the expression of this cluster, reduced renal function, the alloimmune process itself, and other influences on the renal transplant awaits further analysis.

5-Aminolevulinate Synthetase↗

PubMed1986

De novo diabetic nephropathy with functional impairment in a renal allograft.

Recurrence of diabetic nephropathy in the allograft of diabetics with end-stage renal disease who undergo renal transplantation has been reported. We report a case of a patient who underwent cadaveric renal transplantation for end-stage renal disease secondary to chronic glomerulonephritis 13 years ago. He developed steroid-induced, insulin-dependent diabetes mellitus 9 months after transplantation and florid nephrotic syndrome with progressive functional impairment due to biopsy-proven diabetic nephropathy 11 years later. This is, to our knowledge, the first report of de novo diabetic nephropathy in a renal allograft of a patient who was not a diabetic at the time of transplantation. It is suggested that histopathologic changes of diabetes mellitus cannot only recur in a renal allograft, but also can develop de novo and lead to functional impairment and ultimately affect graft survival. In view of increasing patient and graft survival in transplanted diabetic and non-diabetic patients, it is reasonable to anticipate an increased incidence of this complication.

Biopsy↗